RESUMO
Failures to produce neutralizing antibodies upon HIV-1 infection result in part from B-cell dysfunction due to unspecific B-cell activation. How HIV-1 affects antigen-specific B-cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue, we found that expression of the HIV-1 pathogenesis factor NEF in CD4 T cells undermines their helper function and impairs cognate B-cell functions including mounting of efficient specific IgG responses. NEF interfered with T cell help via a specific protein interaction motif that prevents polarized cytokine secretion at the T-cell-B-cell immune synapse. This interference reduced B-cell activation and proliferation and thus disrupted germinal center formation and affinity maturation. These results identify NEF as a key component for HIV-mediated dysfunction of antigen-specific B cells. Therapeutic targeting of the identified molecular surface in NEF will facilitate host control of HIV infection.
Assuntos
Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , Animais , Células HEK293 , HIV-1 , Humanos , Evasão da Resposta Imune/imunologia , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Body dysmorphic disorder (BDD) is a psychiatric disorder defined by an excessive concern about one's physical appearance, especially regarding slight or imagined abnormities of the body. This study was conducted to compare postoperative quality of life (QOL) changes after primary septorhinoplasty among patients screening positive and those screening negative for BDD. Two common instruments for the screening of BDD were used namely the Dysmorphic Concern Questionnaire (DCQ) and the BDD Concern Questionnaire (BDDQ). For the determination of QOL changes, three validated screening instruments were used. The Functional Rhinoplasty Outcome Inventory (FROI-17) and the Rhinoplasty Outcomes Evaluation (ROE) were used as disease-specific instruments and the Short Form 36 Health Survey (SF-36) was used as a general instrument. All patients completed the FROI-17, the ROE, and the SF-36 preoperatively and 60 months postoperatively. The BDD questionnaires were singularly obtained 60 months after surgery. The authors identified 9.8% of our patients with a possible BDD diagnosis. The patients screening positive for BDD showed significantly lower ROE scores postoperatively, compared with those screening negative for BDD. QOL gains detected by the disease-specific instruments (ROE and FROI-17) were only significant in the non-BDD group. No significant QOL gains were detectable with the FROI-17, the ROE, and the SF-36 in the BDD group. In patients screening negative for BDD, QOL, as measured with the SF-36, improved significantly in five categories: physical functioning, role-functioning physical, bodily pain, general health, and social functioning. Patients screening positive for BDD did not improve in any categories of the general SF-36 questionnaire. Instead, their score in the "mental health" category was significantly lower 5 years after their surgery compared with preoperatively. Patients retrospectively screening positive for BDD in our cohort did not improve in QOL postoperatively. Alternative nonsurgical treatments such as cognitive behavioral treatment and/or selective serotonin reuptake inhibitors have been reported to be effective and should be considered as the treatment of choice. Some studies suggest that a smaller subgroup of BDD patients may benefit from functional rhinoplasty. Further research and larger long-term prospective outcome studies are needed to understand the influence of BDD symptoms on postoperative satisfaction and QOL changes after septorhinoplasty.
Assuntos
Transtornos Dismórficos Corporais/psicologia , Septo Nasal/cirurgia , Qualidade de Vida , Rinoplastia , Adolescente , Adulto , Transtornos Dismórficos Corporais/diagnóstico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Período Pós-Operatório , Período Pré-Operatório , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários , Adulto JovemRESUMO
INTRODUCTION: The assessment of outcomes in aesthetic rhinoplasty is highly relevant because patient satisfaction and improved health-related quality of life (QoL) are the predominant factors in determining success. The patient-reported outcome measures (PROMs) employed in rhinoplasty research studies are remarkably diverse, thus yielding difficulties with data analysis. The aim of this article is to provide a comprehensive review of the literature to reveal the relevance of the QoL assessment for rhinosurgeons. METHODS: A systematic literature search with the terms "Rhinoplasty" and "Quality of Life" was conducted using PubMed/MEDLINE, Google Scholar and Cochrane databases. Primarily, all publications related to QoL following aesthetic rhinoplasty between 2002 and 2017 were identified. As a secondary selection, we focused on articles with a prospective study design, a significant cohort size (at least 50 patients) and a follow-up period of at least 6 months after aesthetic rhinoplasty. RESULTS: A total of 62 PROM studies assessing QoL following aesthetic rhinoplasties were obtained. We ascertained an increasing publication rate of QoL articles over the last 15 years. Only 17 studies satisfied comprehensive inclusion criteria of a high qualitative study selection. The Rhinoplasty Outcome Evaluation was the most frequently used QoL questionnaire of the secondary selection (70.6%). The total number of 16 various questionnaires exhibit high heterogeneity. CONCLUSION: Our data strengthen the increasing importance of the assessment of QoL after rhinoplasty. Despite a lack of reliable publications with considerable heterogeneity and large variability in outcomes, functional-aesthetic rhinoplasty leads to a significant improvement of patient's health-related QoL. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Assuntos
Satisfação do Paciente , Qualidade de Vida , Rinoplastia/métodos , Rinoplastia/psicologia , Feminino , Humanos , Masculino , Nariz/cirurgia , Medidas de Resultados Relatados pelo Paciente , Medição de Risco , Cirurgia Plástica/métodos , Cirurgia Plástica/psicologia , Resultado do Tratamento , Estados UnidosRESUMO
Transplant recipients frequently exhibit an increased Epstein-Barr virus (EBV) load in the peripheral blood. Here, we quantitated the EBV-infected cells in the peripheral blood of these patients and defined the mode of viral infection, latent or lytic. These data indicated that there is no strong correlation between the number of infected cells and the EBV load (EBVL). This can be explained by a highly variable number of EBV copies per infected cell and by lytic replication in some cells. The plasma of these patients did not contain any free infectious viruses, but contained nevertheless EBV DNA, sometimes in large amounts, that probably originates from cell debris and contributed to the total EBVL. Some of the investigated samples carried a highly variable number of infected cells in active latency, characterized by an expression of the Epstein-Barr nuclear antigens (EBNA2) protein. However, a third of the samples expressed neither EBNA2 nor lytic proteins. Patients with an increased EBVL represent a heterogeneous group of patients whose infection cannot be characterized by this method alone. Precise characterization of the origin of an increased EBVL, in particular, in terms of the number of EBV-infected cells, requires additional investigations including the number of EBV-encoded small RNA-positive cells.